OBJECTIVES: ITCs estimate relative treatment effects not compared in head-to-head trials. According to the assumption of transitivity, trials must be comparable on factors including PVs/TEMs; however, these are not always consistently identified.

METHODS: An SLR was conducted across three databases (Embase, MEDLINE, CDSR) to identify ITCs including CAR T-cell therapies. Data on the indication, intervention, identification, PVs/TEMs, and sensitivity analyses were summarized. Abstracts were considered if no associated full-text articles were identified.

RESULTS: 687 publications were identified; 30 ITCs (14 abstracts, 16 articles) on seven hematological malignancies met the inclusion criteria. Five therapies (with overlap between studies) were evaluated: tisagenlecleucel (12), axicabtagene (9), ciltacabtagene (9), lisocabtagene (8), and idecabtagene (5). Most abstracts (71% of 14) did not report how PVs/TEMs were identified, while full-text publications included varied descriptions. PVs/TEMs were identified by statistical ranking (31%), literature review and clinical experts (19%), not reported (19%), clinical experts (13%), or literature review (6%). There was heterogeneity in PVs/TEMs within the same indication and among ITCs evaluating the same CAR-Ts. Common variables between studies included age (22), ECOG status (13), and prior stem-cell transplant (12). Among seven ITCs in RRMM, two ITCs adjusted for sex, and one ITC each adjusted for creatine clearance, extramedullary disease, and race. There was no overlap in PVs/TEMs among seven ITCs in DLBCL (including two ITCs comparing lisocabtagene to tisagenlecleucel; four ITCs comparing axicabtagene to lisocabtagene). Sensitivity analysis may account for the variable use of different PVs/TEMs between studies; however, less than half of the ITCs (13/30) reported sensitivity analysis.

CONCLUSIONS: This case study identified a lack of transparency in the identification of PVs/TEMs and inconsistencies in the ways PVs/TEMs are incorporated into ITCs. There is a need for guidance on the identification of PVs/TEMs which would reduce bias in the ITC results and increase confidence in decision-making.